Pyrroloquinoline quinone (PQQ) is a natural product and is also known as methoxatin. Among many applications, primary use of PQQ is to protect mitochondria from oxidative stress, providing neuroprotection and cardioprotection. Common food sources of PQQ are parsley, green pepper, green tea, papaya, kiwi and milk. However, the available concentrations of PQQ in the food sources are only in picomolar (pM) to nanomolar (nM) levels. This necessitates the development of chemical processes which can produce large quantities of PQQ for everyday consumption.
The first complete synthesis of PQQ was reported by Corey et al. (1981). As per the Corey's publication, PQQ was synthesized in milligram (mg) scale and the numbers of steps involved in the synthesis of PQQ from commercially available starting material were ten.
Later, the synthesis of PQQ by a nine step-method was reported by Martin et al. (1993). However, the synthetic route described here is very similar to the aforementioned Corey's method and isolation of the final compound involves very complex and laborious process.
Kempf et al., (WO2006/102642A1) describes the synthesis of PQQ. This application mainly discloses the large scale synthesis of PQQ via a combination of Corey's and Martin's route. This application further claims the purification of final compound with sulphuric acid. However, the synthesis method involves large number of steps and the isolation of advanced intermediates further involves tedious labor intensive procedures. Hence, it can be observed that there is a need for better and simpler synthetic method for obtaining Pyrroloquinoline quinone (PQQ).